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Biomedical subjects

M Oravec

Publications and source records attributed to M Oravec.

16 recordsLinked to original sources

Hypothalamic-pituitary dopaminergic function in hepatic failure in man.

The growth hormone (GH) response to apomorphine HCl (Apo) (0.75 mg sc), a dopamine (DA) receptor agonist, was assessed in healthy chronic alcoholics without cirrhosis (N = 20) and in patients with alcoholic cirrhosis both with (N = 5) and without (N = 14) hepatic encephalopathy (HE). A significant number of cirrhotic patients with (P less than 0.004) and without (P less than 0.002) HE had an impaired GH response (peak increment less than 5 ng/ml) compared with non-cirrhotic individuals. An impaired GH response was independent of the presence of HE. The magnitude of the GH response was unrelated to plasma oestrone, oestradiol, or progesterone concentrations but was significantly correlated with plasma testosterone levels (P less than 0.01). None of the patients with an abnormally low testosterone concentration showed a normal GH response. None of the subjects with HE showed an arousal response to Apo. These results suggest that DA receptor sensitivity is decreased in liver cirrhosis and that this decrease is related to inadequate circulating levels of testosterone. The occurrence of HE is independent of impaired DA function. The present study only evaluates DA function in the hypothalamic-pituitary axis and therefore may not reflect changes in other regions of brain.

Alcoholism

The effect of growth hormone on the metabolism of a tryptophan load in the liver and brain of hypophysectomized rats.

Growth hormone antagonizes the induction of tryptophan pyrrolase and tyrosine amino-transferase by cortisol. We have shown that contrary to previous reports, growth hormone is also capable of antagonizing the induction of these enzymes by tryptophan and alpha-methyl tryptophan. As alpha-methyl tryptophan is not metabolized appreciably in the rat, our data show that growth hormone does not act indirectly through changes in the liver tryptophan content as was suggested previously. Growth hormone decreases the rate of tryptophan catabolism in vivo after induction of tryptophan pyrrolase by tryptophan and alpha-methyl tryptophan. Because the rate of catabolism of a tryptophan is slower in animals treated with growth hormone, tissue tryptophan levels and the rate of synthesis of 5-hydroxyltryptamine in the brain are higher in these animals than in those receiving tryptophan alone. Thus, although tryptophan administration raises brain 5-hydroxytryptamine levels, induction of tryptophan pyrrolase in the liver, by the load, limits the extent and duration of the rise in brain 5-hydroxytryptamine synthesis. This has important implications for the clinical use of tryptophan in psychiatric disorders, where tryptophan is given to produce long-lasting elevations of brain 5-hydroxytryptamine.

Animals

Stimulation of tyrosine aminotransferase activity by dl-alpha-methyltryptophan.

DL-alpha-Methyltryptophan (alphaMeTrp), a synthetic analogue of tryptophan, has been found to be a potent inducer of hepatic tyrosine aminotransferase activity in the adrenalectomized rat. alphaMeTrp is inactive in vitro. Unlike the action of other known inducers (tryptophan, hydrocortisone, adenosine cyclic 3:5-monophosphate, and glucagon), maximal stimulation of enzyme activity occurs only 16 to 30 hours after alphaMeTrp administration and the activity is still elevated at 96 hours. Only the L isomer of alphaMeTrp is active, and addition of a hydroxyl group to position 5 of the indole ring renders an inactive compound. The induction can be prevented by actinomycin D or cycloheximide but not galactosamine. Administration of alphaMeTrp together with hydrocortisone produced an additive stimulation of enzyme activity. alphaMeTrp given along with glucagon or adenosine cyclic 3:5-monophosphate caused a further but not additive increase in enzyme activity. Tryptophan given along with alphaMeTrp promoted no extra stimulation whatsoever. These data indicate that alphaMeTrp and tryptophan may act via a common pathway which in part requires RNA synthesis. Other enzymes, namely alanine and aspartate aminotransferase, ornithine aminotransferase, ornithine carbamoyltransferase, serine dehydratase, and histidine ammonialyase, were not affected by treatment of rats with alphaMeTrp.

Adrenalectomy